Currently, there is no treatment that can halt disease progression, so therapies focus on managing the symptoms, which include gait instability, lack of coordination, and involuntary movements. However, treatments that target the source of the disease and increase frataxin levels in affected individuals are urgently needed.

In the study, researchers aimed at accelerating the development of a therapy for Friedreich’s ataxia by using a drug repositioning approach. This consists on finding a new application for a previously approved treatment, usually reducing the time for therapies to reach patients, as the information about dosage and safety is already available.

The authors tested 853 FDA-approved medicines for different conditions to see whether any could increase cellular frataxin levels.

They found 19 compounds that potentially promoted frataxin regulation. The candidates had different modes of action and were used to treat various conditions. Because FA is a lifelong disease, researchers focused on treatments that were well-tolerated when used for long periods of time.

The best candidate was etravirine, an anti-viral treatment approved by the FDA in 2008 for the treatment of HIV. “Etravirine is safe and well-tolerated over a long-term regimen and is currently prescribed as a lifelong treatment for HIV-positive patients, starting from 6 years of age,” the authors stated.

The researchers treated cells extracted from FA patients with etravirine and found that the treatment increased frataxin in about 50% within 24 hours and that the increased levels were maintained for over 96 hours.

The treated cells accumulated frataxin to levels similar to those produced by the cells of the patients’ unaffected mothers. This suggests that the treatment could be therapeutically significant. Etravirine increased frataxin levels by specifically inducing the production of the RNA that codifies the protein.

Cells of FA patients are deficient in proteins containing iron and sulfur (iron-sulfur cluster) and are very susceptible to oxidative stress. Treatment with etravirine restored the levels of members of the iron-sulfur cluster and conferred resistance to oxidative stress. Furthermore, treated cells did not show any sign of toxicity.

“Here we show, for the first time, that the antiviral drug etravirine is able to promote frataxin accumulation in cells derived from [FA] patients, restoring physiological frataxin levels,” the authors said.

“Considering its excellent safety profile along with its ability to increase frataxin levels and correct some of the disease-related defects, etravirine represents a promising candidate as a therapeutic for Friedreich’s ataxia,” the researchers said. “Our data strongly encourage further evaluation of etravirine [in the treatment of this disease].”